Three-Component Alkene Difunctionalization by Direct and Selective Activation of Aliphatic C-H Bonds

Catalytic alkene difunctionalization is a powerful strategy for the rapid assembly of complex molecules and has wide range of applications in synthetic chemistry. Despite significant progress, a compelling challenge that still needs to be solved is the installation of highly functionalized C(sp(3))-hybridized centers without requiring pre-activated substrates. We herein report that inexpensive and easy-to-synthesize decatungstate photo-HAT, in combination with nickel catalysis, provides a versatile platform for three-component alkene difunctionalization through direct and selective activation of aliphatic C-H bonds. Compared with previous studies, the significant advantages of this strategy are that the most abundant hydrocarbons are used as feedstocks, and various highly functionalized tertiary, secondary, and primary C(sp(3))-hybrid centers can be easily installed. The practicability of this strategy is demonstrated in the selective late-stage functionalization of natural products and the concise synthesis of pharmaceutically relevant molecules including Piragliatin.

Automated summary

Catalytic alkene difunctionalization using decatungstate photo-HAT and nickel catalysis allows for the direct activation of aliphatic C-H bonds, enabling the installation of highly functionalized C(sp(3))-hybrid centers. This strategy demonstrates practicality in selective late-stage functionalization of natural products and concise synthesis of pharmaceutically relevant molecules.